We propose to investigate the nature and chromosomal localization of genes or chromosomal regions associated with childhood cancers as heritable germline mutations or as acquired somatic mutations. We will investigate 100-150 blood samples per year from patients with childhood cancer and congenital anomalies, familial childhood cancer, and/or multiple primary tumors, and their relatives utilizing high resolution chromosomal banding and complementary biochemical, immunologic and chromosomal polymorphic genetic markers. These methods should permit identification of regions of gross chromosomal deletion, triplication, or rearrangement of submicroscopic deletion or triplication demonstrable by gene dose effect and of mapping of cancer-predisposing genes in families. These findings should indicate the frequence of grossly detectable chromosomal anomalies in patients with a probable genetic form of childhood cancer, and may help to determine whether the same chromosomal regions which predispose to childhood cancer in chromosomal deletion cases are involved in apparent autosomal dominant childhood cancer predisposition without gross chromosomal deletion. In addition, we would utilize similar techniques to study tumor genotypes, to determine whether the same chromosomal regions are deleted, duplicated or altered in function in somatic (tumor) cells in individuals with a normal constitutional karyotype. Identification of specific chromosomal regions consistently associated with a childhood cancer predisposition would provide not only an opportunity for genetic counseling and detection of high risk individuals in families but also an opportunity for in-vitro investigation of the molecular nature of genes and gene products which predispose to childhood cancer.